Document text
Principal Investigator: Elizabeth Anne Thompson
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2024
Award: $162,000
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
This is a proposal for a two-year career transition award to study atypical B cells as a novel immunologic and
metabolic target to improve vaccine responses in immunosuppressed individuals. The candidate is currently a
postdoctoral research fellow at the Johns Hopkins University School of Medicine. The proposal builds on the
candidate's extensive experience in vaccine immunology and immunometabolism to understand how metabolic
reprogramming of B cells contributes to successful vaccine responses. The COVID-19 pandemic has highlighted
the need to develop and rapidly deploy highly immunogenic vaccines. However, insufficient immune responses
in immunocompromised individuals have emphasized that novel vaccine formulations may be required for
specific populations to overcome immunosuppression. To date, the basic immunology behind successful
vaccine responses during immunosuppression has not been well characterized. By dissecting the immunologic
and metabolic landscape following vaccination in immunosuppressed individuals, we hope to generate building
blocks to reverse engineer vaccines for specific patient populations. Preliminary data from the principal
investigator indicates that solid organ transplant recipients, who respond poorly to vaccination due to a variety
of immunosuppressive drugs, manage to successfully respond to COVID-19 vaccination by expanding atypical
B cells that are reliant on fatty acid oxidation. To further these findings, the principal investigator has proposed
a research plan consisting of 3 specific aims. Aim 1 will define populations of immunosuppressed individuals
who utilize atypical CD11c+ B cells as a salvage pathway to successful vaccine responses. Aim 2 will assess
atypical CD11c+ B cell and T cell interaction to determine specific immunological contexts that drive CD11c+ B
cell expansion. Aim 3 will target fatty acid oxidation using vaccine adjuvants to enhance atypical CD11c+ B cell
development. Together, these studies will answer how atypical B cells develop in the presence of
immunosuppression, what agents we can use to metabolically target them, and who will benefit from vaccine
strategies targeting atypical B cells. The principal investigator will also learn new techniques necessary to
accomplish the proposed research under the advisory team (Drs. Cox, Bailey, Durbin, Ji, and Pearce), all of
whom have pioneering expertise in vaccinology, immunology, immunometabolism, and biostatistics. Importantly,
her advisory committee collectively has a very strong track record of training both clinical and postdoctoral fellows
who have successfully transitioned into independent investigators at top tier research institutions. She will also
engage in and present at national seminars, take coursework on metabolic modeling, clinical vaccinology, Jr.
Faculty leadership program, grant-writing seminars, and training on running a laboratory. The outlined career
development and research plan will provide the candidate with unique cross-disciplinary skills that will enable
her transition to independence and identify promising strategies to improve vaccine responses in
immunocompromised individuals.
Terms: <AIDS Virus><Ab response><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Address><Advisory Committees><Antibody Formation><Antibody Production><Antibody Response><Antigen Presentation><Automobile Driving><B Cell Proliferation><B blood cells><B cell><B cells><B-Cell Activation><B-Cell Development><B-Cells><B-Lymphocytes><B-cell><Biometrics><Biometry><Biostatistics><CD11c><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 vaccination><COVID-19 years><Career Transition Award><Cell Body><Cell Communication><Cell Count><Cell Function><Cell Interaction><Cell Number><Cell Physiology><Cell Process><Cell-to-Cell Interaction><Cells><Cellular Function><Cellular Physiology><Cellular Process><Clinical><Communicable Diseases><Data><Development><Development and Research><Doctor of Philosophy><Drugs><Elderly><Faculty><Fatty Acids><Frequencies><Future><Goals><Grant><Groups at risk><HIV><Hematologic Cancer><Hematologic Malignancies><Hematologic Neoplasms><Hematological Malignancies><Hematological Neoplasms><Hematological Tumor><Hematopoietic Cancer><Human Immunodeficiency Viruses><ITGAX><ITGAX gene><Immune response><Immune system><Immunochemical Immunologic><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunology><Immunology procedure><Immunosuppressants><Immunosuppressed Host><Immunosuppression><Immunosuppression Effect><Immunosuppressive Agents><Immunosuppressive Effect><Immunosuppressive drug><Immunosuppressive treatment><In Vitro><Individual><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Institution><Investigators><Knowledge><LAV-HTLV-III><Laboratories><Leadership><Learning><Lipids><Lymphadenopathy-Associated Virus><Malignant Hematologic Neoplasm><Medication><Metabolic><Metabolic Pathway><Methods><Mitochondria><Modeling><Pathway interactions><Patients><People at risk><Persons><Persons at risk><Ph.D.><PhD><Pharmaceutical Preparations><Phenotype><Population><Populations at Risk><Postdoc><Postdoctoral Fellow><Principal Investigator><Proliferating><Qualifying><R & D><R&D><Regimen><Research><Research Associate><Research Personnel><Researchers><Reverse engineering><Role><Running><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 vaccination><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Sampling><Scientist><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 vaccination><Solid><Subcellular Process><System><T memory cell><T-Cell Activation><T-Cells><T-Lymphocyte><Task Forces><Techniques><Technology><Testing><Training><Universities><Up-Regulation><Upregulation><Vaccination><Vaccine Adjuvant><Vaccines><Virus-HIV><Work><Writing><activate T cells><activated B cells><advanced age><advisory team><antibody biosynthesis><career development><cohort><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 vaccination><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><defined contribution><developmental><driving><drug/agent><expectation><experience><fat metabolism><fatty acid oxidation><geriatric><global health><high dimensional data><host response><immune suppression><immune suppressive activity><immune suppressive agent><immune suppressive function><immune suppressor><immune system response><immunogenic><immunoglobulin biosynthesis><immunologic assay><immunologic assay/test><immunoresponse><immunosuppressed><immunosuppressed patient><immunosuppressive activity><immunosuppressive function><immunosuppressive response><immunosuppressive substance><immunosuppressor><improved><insight><lipid metabolism><long chain fatty acid><medical college><medical schools><memory T lymphocyte><mitochondrial><mitochondrial metabolism><multidimensional data><multidimensional datasets><new vaccines><next generation vaccines><novel><novel vaccines><organ transplant patient><organ transplant recipient><oxidation><oxidized lipid><pathway><patient population><pharmacologic><post-doc><post-doctoral><post-doctoral trainee><programs><research and development><research associates><response><school of medicine><senior citizen><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><skills><social role><thymus derived lymphocyte><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccine antibodies><vaccine formulation><vaccine induced antibodies><vaccine response><vaccine responsiveness><vaccine strategy><vaccine-induced antibodies><vaccine-induced response><vaccinology>